Renal-protective effect of thalidomide in streptozotocin-induced diabetic rats through anti-inflammatory pathway

Background: Diabetic nephropathy (DN) is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats. Methods: Male Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes. Diabetic rats were treated with thalidomide (200 mg/kg/d) for 8 weeks, and then blood and urine were collected for measurement of renal function-related parameters. Histopathology, immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analyses were performed to assess renal proinflammatory cytokines, fibrotic protein, and related signaling pathways. Results: Diabetic rats exhibited obvious renal structural and functional abnormalities, as well as renal inflammation and fibrosis. Compared with diabetic control rats, those treated with thalidomide showed significantly improved histological alterations and biomarkers of renal function, as well as reduced expression of renal inflammatory cytokines, including NF-kappa B and MCP-1. Furthermore, renal fibrotic proteins, such as TGF-beta 1, T beta RII, T beta RI, smad3, collagen IV, and fibronectin were also remarkably suppressed. Treatment with thalidomide markedly stimulated the phosphorylation of AMPK alpha. Conclusion: In this study, thalidomide suppressed the inflammatory and fibrotic processes in DN. These effects were partly mediated by the activation of AMPKa, and inhibition of the NF-kappa B/MCP-1 and TGF-beta 1/Smad signaling pathways. These results suggest that thalidomide may have therapeutic potential in diabetic renal injury through the anti-inflammatory pathway.